Shifts in the metabolic program of hepatocytes occur when these cells are stimulated to divide during compensatory or neoplastic growth. Because messenger RNAs (mRNA) exert a controlling role in many cellular functions it is likely that alterations in mRNA populations are related to changes in the growth capacity of hepatocytes. We have determined in normal and hypertrophic rat livers: a) the sequence complexity of polysomal mRNA; b) the relatve abundance of mRNA classes; c) the sequence homology between mRNA populations and d) the proportion of the genome expressed. The results indicate that liver hypertrophy does not appear to require the expression of a larger proportion of the non-repetitive genome. However, more subtle alterations involving 10-15 percent of polysomal mRNA are detectable. We propose to extend our studies by analysing in detail the genomic expression in hyperplastic livers following partial hepatectomy and in neoplastic nodules produced in the liver of rats fed the carcinogen N-2-fluorenylacetamide (2-FAA). Our goal is to determine the extent to which mRNA populations in normal, compensatory and neoplastic growth of rat liver differ qualitatively and quantitatively from each other. We hope to identify alterations in mRNA populations which are specific for neoplastic transformation and to distinguish these alterations from those which take place in hypertrophic and hyperplastic livers.